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Summary: Self‐incompatibility plays a vital role in angiosperms, by preventing inbreeding depression and maintaining genetic diversity within populations. Following polyploidization, many angiosperm species transition from self‐incompatibility to self‐compatibility.Here, we investigated the S‐locus in Brassicaceae and identified distinct origins for the sRNA loci, SMI and SMI2 (SCR Methylation Inducer 1 and 2), within the S‐locus. The SMI loci were found to be widespread in Cruciferae, whereas the SMI2 loci were exclusive to Brassica species.Additionally, we discovered four major S‐haplotypes (BnS‐1, BnS‐6, BnS‐7, and BnS‐1300) in rapeseed. Overexpression of BnSMI‐1 in self‐incompatible Brassica napus ('S‐70S1300S6') resulted in a significant increase in DNA methylation in the promoter regions of BnSCR‐6 and BnSCR‐1300, leading to self‐compatibility. Conversely, by overexpressing a point mutation of BnSmi‐1 in the 'S‐70S1300S6' line, we observed lower levels of DNA methylation in BnSCR‐6 and BnSCR‐1300 promoters. Furthermore, the overexpression of BnSMI2‐1300 in the 'SI‐326S7S6' line inhibited the expression of BnSCR‐7 through transcriptional repression of the Smi2 sRNA from the BnS‐1300 haplotype.Our study demonstrates that the self‐compatibility of rapeseed is determined by S‐locus sRNA‐mediated silencing of SCR after polyploidization, which helps to further breed self‐incompatible or self‐compatible rapeseed lines, thereby facilitating the utilization of heterosis. [ABSTRACT FROM AUTHOR]

This study was undertaken to elucidate the mechanism underling the protective effect of a high saturated fat (HSF) diet against the development of alcoholic fatty liver in mice. We tested the effects of a HSF diet on the ethanol-mediated increase in hepatic sterol regulatory element binding protein 1 (SREBP-1) activity. Thirty-two male mice were divided into 4 groups and fed liquid diets consisting of either a high polyunsaturated fat (40% of energy from corn oil) or a HSF (40% of energy from cocoa butter) diet with or without ethanol for 4 wk. In the ethanol-containing diets, ethanol was substituted for an equivalent amount of carbohydrate to provide 27.5% of the total energy. Control mice were pair-fed the same volume of liquid diets as the ethanol-fed mice. The HSF diet suppressed the increase in mature SREBP-1 protein and prevented increased mRNA of the SREBP-l-regulated lipogenic enzymes in the ethanol-fed mice (P < 0.05). Sirtuins 1 (SIRT1), a [NAD.sup.+]-dependent class III histone deacetylase, was upregulated by ethanol administration in mice fed the HSF diet (P < 0.05). The HSF diet blocked histone H3 at lysine 9 (lys9) hyperacetylation and attenuated association of acetylated histone H3-Lys9 with the promoters of mitochondrial glycerol-3-phosphate acyltransferase and stearoyl-CoA desaturase 1 in the livers of the ethanol-fed mice. These results suggest that the protective effects of HSF diet against the development of alcoholic liver steatosis may occur via regulation of the hepatic SIRT1-SREBP-l-histone H3 axis, suppressing the expression of genes encoding lipogenic enzymes and slowing the synthesis of hepatic fatty acids.

Objective We aimed to identify key susceptibility gene targets in multiple datasets generated from postmortem brains and blood of Parkinson's disease (PD) patients and healthy controls (HC). Methods We performed a multitiered analysis to integrate the gene expression data using multiple-gene chips from 244 human postmortem tissues. We identified hub node genes in the highly PD-related consensus module by constructing protein–protein interaction (PPI) networks. Next, we validated the top four interacting genes in 238 subjects (90 sporadic PD, 125 HC and 23 Parkinson's Plus Syndrome (PPS)). Utilizing multinomial logistic regression analysis (MLRA) and receiver operating characteristic (ROC), we analyzed the risk factors and diagnostic power for discriminating PD from HC and PPS. Results We identified 1333 genes that were significantly different between PD and HCs based on seven microarray datasets. The identified MEturquoise module is related to synaptic vesicle trafficking (SVT) dysfunction in PD (P  < 0.05), and PPI analysis revealed that SVT genes PPP2CA, SYNJ1, NSF and PPP3CB were the top four hub node genes in MEturquoise (P  < 0.001). The levels of these four genes in PD postmortem brains were lower than those in HC brains. We found lower blood levels of PPP2CA, SYNJ1 and NSF in PD compared with HC, and lower SYNJ1 in PD compared with PPS (P  < 0.05). SYNJ1, negatively correlated to PD severity, displayed an excellent power to discriminating PD from HC and PPS. Conclusions This study highlights that SVT genes, especially SYNJ1, may be promising markers in discriminating PD from HCs and PPS. [ABSTRACT FROM AUTHOR]

Abstract Background Enzymatic biodiesel production by transesterification in solvent media has been investigated intensively, but glycerol, as a by-product, could block the immobilized enzyme and excess n-hexane, as a solution aid, would reduce the productivity of the enzyme. Esterification, a solvent-free and no-glycerol-release system for biodiesel production, has been developed, and two-step catalysis of soybean oil, hydrolysis followed by esterification, with Yarrowia lipolytica lipase is reported in this paper. Results First, soybean oil was hydrolyzed at 40°C by 100 U of lipase broth per 1 g of oil with approximately 30% to 60% (vol/vol) water. The free fatty acid (FFA) distilled from this hydrolysis mixture was used for the esterification of FFA to fatty acid ethyl ester by immobilized lipase. A mixture of 2.82 g of FFA and equimolar ethanol (addition in three steps) were shaken at 30°C with 18 U of lipase per 1 gram of FFA. The degree of esterification reached 85% after 3 hours. The lipase membranes were taken out, dehydrated and subjected to fresh esterification so that over 82% of esterification was maintained, even though the esterification was repeated every 3 hours for 25 batches. Conclusion The two-step enzymatic process without glycerol released and solvent-free demonstrated higher efficiency and safety than enzymatic transesterification, which seems very promising for lipase-catalyzed, large-scale production of biodiesel, especially from high acid value waste oil.

Objective: We perform this meta-analysis was to evaluate the efficacy of neoadjuvant chemotherapy followed by radiation in the treatment of locally advanced nasopharyngeal carcinoma.Materials and Methods: We searched the database of Medline and Wanfang to screen and included the prospective, randomized controlled trials of neoadjuvant chemotherapy plus radiation versus radiotherapy in the treatment of locally advanced nasopharyngeal carcinoma. The pooled 5-year overall survival, 5 years disease free survival, recurrence rate, and metastasis rate were calculated by Stata version 11.0 statistical software.Results: Five prospective clinical studies were included in this meta-analysis. The total number of cases included in this study was 1277. The pooled 5 years overall survival and 5 years disease free survival were not statistical different between the neoadjuvant chemotherapy plus radiation group and radiotherapy group, respectively (P > 0.05). But the recurrence rate (odds ratio [OR] = 0.65, P < 0.05) and metastasis rate (OR = 0.61, P < 0.05) were significantly lower in the neoadjuvant chemotherapy plus radiation group compared to radiotherapy group.Conclusion: Neoadjuvant chemotherapy followed by radiation can decrease the risk of recurrence and metastasis but not improve the 5 years overall survival and 5 years disease free survival compared to radiotherapy alone in the patients with locally advanced nasopharyngeal carcinoma. [ABSTRACT FROM AUTHOR]

We have reported that hyperglycemia is associated with reduction of neuronal size and reduced long-term spatial memory in the developing brain of streptozotocin diabetic (STZ-D) rats. We have also noted that recurrent hypoglycemia in age matched developing rat brains does not effect cell size or long-term memory. We have also shown that diabetes is associated with increased intracellular sorbitol and reduced taurine in the rat brain. Taurine is a cellular osmole regulator that counteracts the increased cellular osmoles associated with elevated sorbitol. Taurine is also a neurotrophic factor that stimulates neuronal growth. Objective: An aldose reductase inhibitor (sorbinil) was given to STZD rats to determine whether it would reduce polyol pathway activity and thereby increase intracellular taurine in the brain. Long-term spatial memory was also tested in these animals. Methods Male Wistar rats 4 weeks of age (100 g) were used. Control rats (10) were compared to STZ-D rats (10) and STZ-D rats receiving 65 mg/kg of oral sorbinil (STZ-D+S) (10) daily for 8 weeks. After 8 weeks of hyperglycemia each of the rats had long-term spatial memory tested using a radial-arm water maze. Brains were removed for measurement of sorbitol and taurine which were expressed as a function of tissue DNA. HbA1c was measured as an indicator of the degree of hyperglycemia. Results: The HbA1c levels of the STZ-D (8.2 ± 0.4), STZ-D+S (7.9 ± 0.3) rats were higher than controls (3.3 ± 0.0). Peripheral hyperglycemia was associated with increased brain sorbitol (0.14±0.02 vs 0.03±0.00lµg/ µg DNA) p<0.001, and reduced taurine (0.65±0.11 vs 1.3±0.09 mg/ µg DNA) p<0.001. Rats receiving Sorbinil had a reduction of cellular sorbitol (0.05 ± 0.001 vs 0.14 ± 0.02) p<0.01 and an increase in cellular taurine (1.26 ± 0.09 vs 0.65 ± 0.11) p<0.01. Long-term spatial memory following normal learning in the hyperglycemic animals was significantly impaired at 24 hours but was normal after receiving Sorbinil during 8 weeks of hyperglycemia. These animals also had normal cellular sorbitol and taurine. Conclusion: The reduced cognitive function associated with hyperglycemia in rats is corrected by inhibition of the polyol pathway and normalization of brain sorbitol and taurine without correcting the extracellular hyperglycemia. [ABSTRACT FROM AUTHOR]

Cervical cancer, primarily squamous cell carcinoma, is the most prevalent gynecologic malignancy. Organoids can mimic tumor development in vitro, but current Matrigel inaccurately replicates the tissue-specific microenvironment. This limitation compromises the accurate representation of tumor heterogeneity. We collected para-cancerous cervical tissues from patients diagnosed with cervical squamous cell carcinoma (CSCC) and prepared uterine cervix extracellular matrix (UCEM) hydrogels. Proteomic analysis of UCEM identified several tissue-specific signaling pathways including human papillomavirus, phosphatidylinositol 3-kinase-AKT, and extracellular matrix receptor. Secreted proteins like FLNA, MYH9, HSPA8, and EEF1A1 were present, indicating UCEM successfully maintained cervical proteins. UCEM provided a tailored microenvironment for CSCC organoids, enabling formation and growth while preserving tumorigenic potential. RNA sequencing showed UCEM-organoids exhibited greater similarity to native CSCC and reflected tumor heterogeneity by exhibiting CSCC-associated signaling pathways including virus protein-cytokine, nuclear factor κB, tumor necrosis factor, and oncogenes EGR1, FPR1, and IFI6. Moreover, UCEM-organoids developed chemotherapy resistance. Our research provides insights into advanced organoid technology through native matrix hydrogels.

Background: Asthenozoospermia is a major factor contributing to male infertility. The mitochondrial sheath (MS), an important organelle in the midpiece of spermatozoa, is crucial to sperm motility. ARMC12 is a mitochondrial peripheral membrane protein. Deletion of Armc12 impairs the arrangement of MS and causes infertility in mice. However, the role of ARMC12 in human asthenozoospermia remains unknown., Objective: To study the genetic defects in patients with asthenozoospermia., Methods: A total of 125 patients with asthenozoospermia and 120 men with proven fertility were recruited. Whole-exome sequencing and Sanger sequencing were performed for genetic analysis. Papanicolaou staining, HE staining, immunofluorescent staining, transmission electron microscopy and field emission scanning electron microscopy were employed to observe the morphological and structural defects of the spermatozoa and testes. Armc12 -knockout mice were generated using the CRISPR-Cas9 system. Intracytoplasmic sperm injection was used to treat the patients., Results: Biallelic ARMC12 mutations were identified in three patients, including homozygous mutations in two siblings from a consanguineous family and compound heterozygous mutations in one sporadic patient. ARMC12 is mainly expressed in the midpiece of elongated and late spermatids in the human testis. The patients' spermatozoa displayed multiple midpiece defects, including absent MS and central pair, scattered or forked axoneme and incomplete plasma membrane. Spermatozoa from Armc12 -/- mice showed parallel defects in the midpiece. Moreover, two patients were treated with intracytoplasmic sperm injection and achieved good outcomes., Conclusion: Our findings prove for the first time that defects in ARMC12 cause asthenozoospermia and multiple midpiece defects in humans., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Alcohol consumption synergistically increases the risk and severity of liver damage in obese patients. To gain insight into cellular or molecular mechanisms underlying the development of fatty liver caused by ethanol-obesity synergism, we have carried out animal experiments that examine the effects of ethanol administration in genetically obese mice. Lean wild-type (WT) and obese (ob/ob) mice were subjected to ethanol feeding for 4 wk using a modified Lieber-DeCarli diet. After ethanol feeding, the ob/ob mice displayed much more pronounced changes in terms of liver steatosis and elevated plasma levels of alanine aminotransferase and aspartate aminotransferase, indicators of liver injury, compared with control mice. Mechanistic studies showed that ethanol feeding augmented the impairment of hepatic sirtuin 1 (SIRT1)-AMP-activated kinase (AMPK) signaling in the ob/ob mice. Moreover, the impairment of SIRT1-AMPK signaling was closely associated with altered hepatic functional activity of peroxisome proliferator-activated receptor γ coactivator-α and lipin-1, two vital downstream lipid regulators, which ultimately contributed to aggravated fatty liver observed in ethanol-fed ob/ob mice. Taken together, our novel findings suggest that ethanol administration to obese mice exacerbates fatty liver via impairment of the hepatic lipid metabolism pathways mediated largely by a central signaling system, the SIRT1-AMPK axis.